Table 1.
Demographics and Baseline Characteristics of CCS, Grouped by Cardiotoxic Exposures, and Sibling Control Subjects
| CCS According to Cardiotoxic Exposure |
||||||
|---|---|---|---|---|---|---|
| All CCS (N = 1,397) | Only Anthracyclines/Mitoxantrone (n = 839a) | Only Radiotherapy to Heart Region (n = 152) | Radiotherapy to Heart Region and Anthracyclines/Mitoxantrone (n = 260a) | Potentially Cardiotoxic Therapyb (n = 143) | Siblings (n = 277) | |
| Demography, diagnosis and treatment history | ||||||
| Sex | ||||||
| Male | 720 (52) | 440 (52) | 74 (49) | 139 (54) | 64 (45) | 112 (40) |
| Female | 677 (49) | 399 (48) | 78 (51) | 121 (47) | 79 (55) | 165 (60) |
| Age at cancer diagnosis, y | 6.1 (0.1-17.9) | 6.2 (0.1-17.9) | 6.1 (0.1-17.0) | 6.9 (0.3-17.9) | 3.9 (0.2-17.3) | — |
| <5 | 595 (43) | 347 (41) | 67 (44) | 97 (37) | 82 (58) | — |
| 5-9 | 396 (28) | 238 (28) | 51 (34) | 71 (27) | 35 (25) | — |
| 10-14 | 317 (23) | 196 (23) | 28 (18) | 71 (27) | 22 (15) | — |
| 15-18 | 89 (6.4) | 58 (6.9) | 6 (3.9) | 21 (8.1) | 4 (2.8) | — |
| Incidence year | — | |||||
| 1963-1969 | 12 (0.9) | 0 (0) | 12 (7.9) | 0 (0) | 0 (0) | — |
| 1970-1979 | 168 (12) | 47 (5.6) | 74 (49) | 21 (8.1) | 26 (18) | — |
| 1980-1989 | 421 (30) | 243 (29) | 32 (21) | 98 (38) | 46 (32) | — |
| 1990-2001 | 796 (57) | 549 (65) | 34 (22) | 141 (54) | 71 (50) | — |
| Primary cancer diagnosis, ICCC-3 | ||||||
| Leukemias, myeloproliferative and myelodysplastic diseases | 566 (41) | 375 (45) | 18 (12) | 88 (34) | 83 (58) | — |
| Lymphomas and reticulo-endothelial neoplasms | 335 (24) | 231 (28) | 24 (16) | 65 (25) | 14 (9.8) | — |
| Central nervous system, intracranial and intraspinal neoplasms | 45 (3.2) | 3 (0.4) | 33 (22) | 2 (0.8) | 7 (4.9) | — |
| Neuroblastoma and other peripheral nervous cell tumors | 48 (3.4) | 23 (2.7) | 16 (11) | 8 (3.1) | 1 (0.7) | — |
| Renal tumors | 167 (12) | 41 (4.9) | 44 (29) | 64 (25) | 18 (13) | — |
| Hepatic tumors | 12 (0.9) | 12 (1.4) | 0 (0) | 0 (0) | 0 (0) | — |
| Bone tumors | 118 (8.4) | 93 (11) | 3 (2.0) | 21 (8.1) | 1 (0.7) | — |
| Soft tissue and other extraosseous sarcomas | 74 (5.3) | 56 (6.7) | 5 (3.3) | 11 (4.2) | 2 (1.4) | — |
| Other, incl. retinoblastoma, germ cell, trophoblastic, gonadal, melanomas and other malignant neoplasms | 32 (2.3) | 5 (0.6) | 9 (5.9) | 1 (0.4) | 17 (11.8) | |
| Anthracycline exposure | 1078 (77) | 818 (98) | 0 (0) | 257 (99) | 0 (0) | — |
| Anthracycline dose, exposed, mg/m2 | 180 (7.7-760) | 180 (7.7-760) | — | 200 (25-720) | — | — |
| 1-100 | 189 (18) | 152 (19) | — | 37 (14) | — | — |
| 101-250 | 560 (52) | 432 (53) | — | 127 (50) | — | — |
| >250 | 324 (30) | 230 (28) | — | 92 (36) | — | — |
| Mitoxantrone exposure | 75 (5.4) | 55 (6.6) | 0 (0) | 20 (7.7) | 0 (0) | — |
| Mitoxantrone dose, exposed, mg/m2 | 40 (10-168) | 44 (10-168) | — | 21 (19-80) | — | — |
| RT to heart region, incl. total body | 412 (30) | 0 (0) | 152 (100) | 260 (100) | 0 (0) | — |
| RT dose to heart region, exposed, Gy | 12 (0.4-99) | — | 13 (0.4-76) | 9.9 (0.4-99) | — | — |
| 0.1-15 | 261 (64) | — | 80 (54) | 181 (70) | — | — |
| 15.1-30 | 95 (23) | — | 53 (36) | 42 (16) | — | — |
| >30 | 51 (13) | — | 14 (9.5) | 37 (14) | — | — |
| Total body irradiation | 83 (6.0) | 0 (0) | 9 (5.9) | 74 (29) | 0 (0) | — |
| Stem cell transplant | 137 (9.9) | 36 (4.3) | 10 (6.8) | 82 (32) | 8 (5.6) | — |
| Cyclophosphamide exposure | 784 (56) | 566 (68) | 37 (24) | 155 (60) | 23 (16) | — |
| Ifosfamide exposure | 211 (15) | 116 (14) | 4 (2.6) | 77 (30) | 14 (9.8) | — |
| Vincristine exposure | 1172 (84) | 716 (85) | 103 (68) | 244 (94) | 106 (74) | — |
| Time since cancer diagnosis, y | 27 (14-55) | 25 (14-48) | 40 (17-55) | 27 (15-45) | 28 (16-49) | — |
| Age at echocardiography, y | 34 (16-65) | 33 (16-61) | 46 (21-65) | 35 (17-59) | 34 (17-64) | 37 (16-59) |
| Questionnaire data | ||||||
| Cardiomyopathy/ heart failure | 47 (3.7) | 27 (3.5) | 3 (2.1) | 17 (7.1) | 0 (0) | 0 (0) |
| Myocardial infarction | 4 (0.3) | 1 (0.1) | 1 (0.7) | 2 (0.8) | 0 (0) | 0 (0) |
| Hypertension | 82 (6.4) | 34 (4.5) | 26 (18) | 14 (6.0) | 8 (6.0) | 2 (0.9) |
| Diabetes | 26 (2.0) | 9 (1.2) | 8 (5.5) | 7 (3.0) | 2 (1.5) | 0 (0) |
| Lipid-lowering medication | 56 (4.0) | 19 (2.3) | 17 (11.2) | 16 (6.2) | 4 (2.8) | 1 (0.4) |
| Ever smoked >1 y | 377 (30) | 234 (31) | 40 (28) | 69 (29) | 33 (25) | 83 (37) |
| Incomplete medical history | 191 | 119 | 17 | 39 | 16 | 92 |
| Outpatient clinic data | ||||||
| Waist circumference, cm | 85 (59-144) | 85 (60-139) | 87 (63-133) | 83 (59-135) | 88 (65-144) | 86 (62-124) |
| Systolic blood pressure, mm Hg | 123 ± 16 | 121 ± 14 | 131 ± 18 | 122 ± 16 | 125 ± 18 | 120 ± 14 |
| Diastolic blood pressure, mm Hg | 75 ± 11 | 74 ± 10 | 78 ± 11 | 75 ± 11 | 75 ± 13 | 73 ± 10 |
| Incomplete physical examination | 44 | 31 | 3 | 8 | 2 | 2 |
Values are n (%), mean ± SD, or median (range). No P values are reported in Table 1 following the STROBE recommendations.
ICCC = International Classification of Childhood Cancer; RT = radiotherapy.
a
Three childhood cancer survivors (CCS) treated with anthracyclines but with missing radiotherapy exposure status could not be classified.
b
Either cyclophosphamide, ifosfamide, or vincristine without anthracyclines, mitoxantrone, or radiotherapy involving the heart region.